- Email: [email protected]
Depth of Anesthesia Monitoring by Bispectral Analysis in Zoo Animals
CHAPTER
19
Depth of Anesthesia Monitoring by Bispectral Analysis in Zoo Animals Jean-Michel Hatt and Olga Martin Jurado
General anesthesia is required in zoological medicine for a variety of reasons, including painful (e.g., surgery) and nonpainful interventions (e.g., radiographic examination). Typically, induction will be achieved via an injectable anesthetic, alone or as a combination. In addition to achieving analgesia and hypnosis, anesthesia in zoological medicine aims at the safe immobilization of the patient over a determined time period. Recovery time is expected to be quick, especially under field conditions, and safe both for the animal and the personnel involved. Monitoring of the patient under general anesthesia is done by a variety of tests. Some of these evaluate hemodynamic functions and autonomic nervous responses, such as heart rate, respiratory rate, blood pressure, and oxygen saturation. Others are intended to measure the depth of anesthesia (DoA) with respect to the degree of hypnosis and analgesia, including measurement of the patient’s reactions to nonphysiologic positions such as dorsal recumbency (righting reflex), corneal and pupillary reflexes, and toe pinch stimulation. In human medicine, DoA measurement is of special importance to avoid occurrence of awareness—that is, the postoperative recollection of events occurring during general anesthesia. In a recent review, incidences of awareness up to 0.2% in adults and up to 0.8% in children were reported.3 In veterinary medicine, the role of awareness cannot be assessed because animals cannot report their postanesthetic experiences. Measurement of DoA is nevertheless of interest from an animal welfare point of view. In zoological medicine, DoA monitoring is of further interest from a personnel and equipment safety point of view. However, the reliability of a stimulation test with regard to the large number of species encountered by the clinician in zoological medicine is at best adequate in relation to safety.
For safety reasons, often a lower than necessary DoA will be chosen, which only prolongs recovery but increases the dose-dependent cardiopulmonary impairment, resulting in an increase of postanesthetic morbidity and mortality. This is reflected by the high anesthetic- and sedative-related risk of death, which ranges in small mammals from 1.4% to 3.6%, in birds from 1.8% to 16.3%, and in reptiles it is 1.5%, compared with dogs and cats (0.1% to 0.2%) and humans (0.02% to 0.01%2). In wildlife anesthesia, mortalities up to 3% have been reported and it was proposed that mortalities above 2% should not be acceptable.1 Established DoA monitors include the bispectral index (BIS, Aspect Medical Systems, Norwood, Mass), the Narcotrend index (Narcotrend Monitor, Schiller AG, Baar, Switzerland), and the state entropy (SE) and response entropy (RE), derived from the spectral entropy from the electroencephalogram (EEG; M-Entropy module, GE Healthcare, Helsinki, Finland). These monitors process the level of corticocerebral activation measured by analog EEGs into a signal that reflects the DoA. The most widely used monitor is the BIS, which in 2004 was used in approximately 34% of all hospital operating rooms in the United States and 78% of teaching institutions, and had a worldwide installation base of over 25,000 units.8 Numerous studies have investigated the BIS. An Internet search on the term bispectral index anesthesia in August 2010 produced over 138,000 results, including a report on the use of the BIS in animals, including the dog, cat, horse, and goat.9 Just like any monitor, the BIS offers possibilities but also has limitations, especially with respect to various drugs. The transposition from a single-species environment such as human medicine to the multitude of species encountered in zoological medicine needs to be done with appropriate care, as with pulse oximetry. 147
148
Section 1 • General
In this chapter, we review the data from studies with BIS measurement in animals and include data on nondomestic animals obtained from studies that were carried out in our laboratory.
BISPECTRAL ANALYSIS METHODOLOGY Bispectral analysis is based on a complex statistical evaluation of human electroencephalographic data that was developed to obtain an index of the level of hypnosis. It uses a Fourier transform, an operation that transforms one complex-valued function of a real variable into another, such as time into frequency. The BIS value is represented as a dimensionless value from 0 (cortical silence) to 100 (awake) (Fig. 19-1). In humans, an
BIS 100
80
60
Awake
Light hypnotic state
Deep sedation
General anaesthesia 40
20
0
Deep hypnotic state
Increasing burst suppression
Cortical silence
Figure 19-1 The bispectral index (BIS) scale is a dimensionless scale from 0 (flatline) to 100 (awake). We used the A-2000-XP Platform Bispectral Index Monitoring System (Aspect Medical Systems, Norwood, Mass). BIS values of 65 to 85 have been recommended for a light hypnotic state, whereas values of 50 to 65 for deep sedation and values of 40 to 50 for general anesthesia are used. BIS values from 40 to 25 have been seen to produce a deep hypnotic state and, with the BIS less than 25, cortical suppression becomes more and more manifest. (From Martin Jurado O: Determination of the Anaesthesia Depth in Chickens with Bispectral Index [BIS]. Ph.D. Thesis, University of Zurich, Zurich, 2008.)
optimal degree of general anesthesia is defined as that associated with a BIS within the range of 40 to 60. In 1996, the U.S. Food and Drug Administration approved the BIS monitor as an accepted measure of the hypnotic effect of anesthetics and sedative drugs in humans. Since its introduction, BIS monitoring has gained increasing popularity in daily anesthesia practice. However, the current evidence indicates various cases of paradoxical BIS changes and inaccurate readings, which also need to be to be taken into consideration when applying the BIS in veterinary medicine (Table 19-1).4,6
TECHNIQUE AND OPTIMUM SETTING The equipment includes a monitor, a digital signal processing cable, and three electrodes with sensors. Newer models include four sensors. It is important to note that the algorithm has been constantly adapted from one model to the other. Therefore, every BIS system will yield different values and the anesthetist needs to be familiar with the system that is being used to interpret changes in values adequately. As with the use of pulse oximetry in zoo animals, the most valuable types of information are the trends indicated by the BIS. The monitor is available as stand-alone system or as an add-on module for most comprehensive patient monitoring systems. Our studies were performed with an A-2000-XP Platform Bispectral Index Monitoring System (Aspect Medical Systems). The sensors were fitted with 24-gauge needles to allow subcutaneous placement instead of the need to shave or pluck the areas, even in small animals. The impedances for sensors 1 and 3 and for sensor 2 were always <7.5 kΩ and <30 kΩ, respectively. Figure 19-2 graphically displays the location of the sensors. Based on the system we used, the different results are displayed in Figure 19-3. The main value is the BIS value, ranging from 0 (flatline or isoelectric EEG) to 100 (awake), which is displayed every 5 seconds. This represents the mean of the maximum and minimum indices of the last 15 or 30 seconds. This smoothing rate needs to be selected in the main menu. In cases of high interference, a longer smoothing rate (30 seconds) is chosen. An important additional value is the suppression ratio (SR), which is the proportion of signals over the last 63-second period for which the electroencephalographic signals are considered to be suppressed or inactive (flatline). It ranges from 0 (no suppression) to 100 (maximal suppression, or isoelectric EEG). Therefore, the lower the value, the better the signal.
Chapter 19 • Depth of Anesthesia Monitoring by Bispectral Analysis in Zoo Animals 149
TABLE 19-1 Effect of Various Factors on Bispectral Index Monitoring in Humans and Horses Effect
Anesthetic Agent Ketamine Detomidine + butorphanol Isoflurane Halothane Clinical Condition Warming blanket Hypoglycemia Hypovolemia Hypothermia Brain death Neuromuscular blocking drugs
BIS Model
BIS Change
Explanation
A-1050, A-2000 A-1000 A-1000 BIS-XP, A-1000
Paradoxical BIS ↑ BIS ↓ Paradoxical BIS ↑ High BIS
β waves ↑, δ waves ↓ In horses α, β waves ↑ Different cortical effect
A-1000, A-2000 A-2000, BIS-XP
BIS BIS BIS BIS BIS BIS
A-1050, A-1000 A-2000 A-1000, A-2000
↑ ↓ ↓ ↓ 0 ↓
Air vibration δ, θ waves ↑, α waves ↓ Cerebral perfusion ↓ Isoflurane enhancement, propofol enhancement Isoelectricity Alleviating electromyogram artifact
Data from Dahaba AA: Different conditions that could result in the bispectral index indicating an incorrect hypnotic state. Anaesth Analg 101:765-773, 2005; and Haga HA, Dolvik NI: Evaluation of the bispectral index as an indicator of degree of central nervous system depression in isofluraneanaesthetized horses. Am J Vet Res 63:438-442, 2002.
Signal quality region
A
B
Bispectral index Graphic display region
D
Figure 19-2 Placement of sensors for bispectral index monitoring in a bird (A, B) and mammal (C, D). Sensor 1 (dot) is placed between the eyes in the frontal area. Sensor 2 (circle) is placed over the temporal musculature. Sensor 3 (X) is placed immediately caudal to the eye angle. (Courtesy Jeanne Peter, Institute of Veterinary Anatomy, University of Zurich, Zurich, Switzerland.)
The quality of the EEG signal is evaluated by combining the signal quality index (SQI) and electromyography (EMG) variables. The SQI is calculated on the basis of impedance data, artifacts, and other variables. It is scaled from 0 (no quality) to 100 (maximal quality). An electromyogram is also scaled from 0 (minimal) to 100 (maximal) and indicates the power in
Waveform box
Menu navigation
C
Suppression ratio
Figure 19-3 Bispectral index monitor. (A-2000-XP Platform Bispectral Index Monitoring System, Aspect Medical Systems, Norwood, Mass.)
the high-frequency range, as well as muscle activity. Interference control is typically achieved by rejecting SQI values under 50% and/or electromyographic values over 50%. The electroencephalographic signal display works with a preset sweep rate of 25 mm/second and a scale of 25 µV/division.
REPTILES The determination of the DoA in reptiles is challenging, as shown in the following examples. The electrical activity of the cortex of Hermann’s tortoises (Testudo
150
Section 1 • General
100
BIS
80 60 40 20 0
0
1
2
4
5
7
8
9 11 12 14 15 17 18 19 21 22 24 25 26 28 29 Time (min)
Figure 19-4 Bispectral index values of a Hermann’s tortoise (Testudo hermanni) during 30 minutes of the intraoperative period, from incision (T0) to the end of the surgery (T30).
hermanni) undergoing anesthesia for soft tissue surgery was evaluated. Following premedication with midazolam (2 mg/kg), butorphanol (0.4 mg/kg), and carprofen (4 mg/kg), anesthesia was induced with intravenous propofol to effect (5-10 mg/kg) and it was maintained with a 1.7% ± 0.7% expiratory fraction of isoflurane. An example of intraoperative BIS recordings is shown in Figure 19-4. In a total of seven Hermann’s tortoises, the BIS was able to display the electrical activity of the cortex during anesthesia—patterns of deep suppression (SR, 80; BIS, 15) combined with bursts of cerebral cortex activation (SR, 0; BIS, 60). This wide fluctuation has been described as a safety mechanism developed to avoid brain damage during brumation in conscious, anoxia-tolerant freshwater turtles and Hermann’s tortoises.5,12 Based on these experiences, the BIS does not seem a helpful adjunct to monitor the depth of anesthesia in chelonians. The electrical activities of the brain of anesthetized snakes (Boa constrictor) and green iguanas (Iguana iguana) have also been monitored with BIS. The first BIS values after induction of anesthesia with intravenous propofol were 70 to 90. In the following minutes and coinciding with isoflurane administration, thus increasing the depth of anesthesia, BIS values decreased to 20 to 30. Depending on titration of isoflurane during the maintenance of anesthesia, BIS values ranged from 30 to 50. Extubation occurred when the animal was considered to be able to breathe spontaneously or when movements of the limbs or the head were observed. In every case, the BIS at this time point ranged from 60 to 85. We found that extubation of the trachea based on the BIS value (BIS ≥ 60) could safely be performed.
However, very close monitoring of the patient is nevertheless recommended. The bispectral index has been found to be a very useful tool when performing anesthesia in a venomous lizard. During a coelioscopic procedure for gender determination, the bispectral index was continuously monitored in a Gila monster (Heloderma suspectum). The mean values of BIS and SR for the 25-minute isoflurane anesthesia were 25 ± 10 and 53 ± 25, respectively. No evident signs of awareness or light plane of anesthesia were observed (i.e., presence of movement, increased respiratory or heart rate). The reason for the lower BIS in the Gila monster versus the iguana and the boa is unknown. It may be hypothesized that venomous or varanid species, to which beaded lizards are related, may undergo deeper planes of anesthesia. In a specific example, the relevance of the BIS during cardiopulmonary resuscitation was assessed during the anesthetic procedure of an adult bearded dragon (Pogona vitticeps) undergoing elective neutering. After premedication with butorphanol (0.4 mg/kg) and meloxicam (0.05 mg/kg), anesthesia was induced with propofol to effect (0.5 mg/kg) and maintained with isoflurane. Intravenous access in the cephalic vein was available. The heart rate (HR) was monitored by Doppler ultrasonography and the respiratory rate (RR) was monitored by counting the excursions of the coelomic cavity. Temperature was maintained with an electric heat blanket. After induction of anesthesia, HR was 44 beats/min, RR was 6 breaths/min, the BIS was 40 and SR was 2. Twenty minutes after induction of anesthesia, the patient moved (HR, 44 beats/min; RR, 4 breaths/min; BIS, 77; SR, 0).
Chapter 19 • Depth of Anesthesia Monitoring by Bispectral Analysis in Zoo Animals 151
Fifteen minutes later, cardiorespiratory arrest occurred; the BIS was 80 and the SR was 0, perhaps related to the unpredictable shunting ability of reptiles. In the following 5 minutes, the surgery was finished while anesthesia was discontinued, ventilation was assisted, heart massage was performed, and aggressive intravenous emergency therapy was administered (atropine, 0.01 mg/kg; epinephrine, 0.02 mg/kg; doxapram, 5 mg/ kg). The mean values of BIS and SR were 90 and 0. Based on BIS (55 ± 18) and SR (13 ± 13) values, the resuscitation effort continued over 20 minutes, although no cardiorespiratory improvements were observed. Within the following 5 minutes, the BIS mean value increased to 90 ± 1 (SR, 0), the heart started to beat (HR, 44 beats/ min) and the patient was able to breathe spontaneously (RR, 4 breaths/min). Extubation of the trachea was performed and the patient recovered from anesthesia. To evaluate the validity of the BIS in bearded dragons, the euthanasia of another patient was monitored. Ten minutes after euthanasia, the BIS decreased to 3 and the SR to 100.
BIRDS The bispectral index has been successfully validated in the avian species using chickens (Gallus gallus) as experimental models.10,13 Median (range) BIS values during anesthesia were 1.75, 1.50, 1.25, 1.00, and 0.75 and the mean anesthetic concentrations of isoflurane were 25% (15% to 35%), 35% (25% to 45%), 35% (20% to 50%), 40% (25% to 55%), and 50% (35% to 65%), respectively. The median BIS value at extubation was 70 ± 9. Blood pressure changed with end-tidal isoflurane concentrations, whereas the heart rate did not. Based on this validation study, the BIS has been further used in clinical avian patients as additional monitoring to assess the degree of hypnosis. Satisfactory results have been obtained in a large variety of orders, such as Anseriformes, Ciconiiformes, Psittaciformes, Falconiformes, and Strigiformes. In an interesting case, the BIS was able to uncover feigning death behavior in a red kite (Milvus milvus) during recovery from isoflurane anesthesia.11 The bispectral index ranged from 44 to 57 during maintenance of isoflurane anesthesia and, at the moment of extubation of the trachea, the BIS was 59. The index rose up to 85 in 1 minute while the kite remained immobile in sternal recumbence. The bird was perched, keeping the upright position. Whereas behavioral or cardiorespiratory variables remained unchanged, the BIS revealed that the bird had regained consciousness.
MAMMALS The anesthesia of three gelada baboons (Theropithecus gelada) for a general examination, tuberculin testing, and radiographic examination were monitored with the BIS. An adequate degree of hypnosis to approach the geladas was achieved after a combination of intramuscular ketamine (5 mg/kg) and medetomidine (0.07 mg/ kg) was administered. During the following 15 minutes, manipulations were carried out without episodes of apparent consciousness while the BIS ranged from 30 to 65. Following reversal with atipamezole, the BIS increased to 97 in the following 8 minutes, coinciding with eye blinking and twitching of facial muscles. Future anesthetic episodes in geladas will benefit from additional monitoring with the BIS because it would increase patient and staff safety (e.g., administration of additional anesthetic drugs before slight movement occurs). The device was able to display a highly accurate state of hypnosis in the presented cases reliably. Similar results were obtained in an orangutan (Pongo pygmaeus) anesthetized with intramuscular ketamine (5 mg/kg) and xylazine (3 mg/kg). Four adult spectacled bears (Tremarctos ornatus) were anesthetized with tiletamine and zolazepam (1.1 to 1.7 mg/kg), and medetomidine (0.06 to 0.1 mg/kg). Three of the bears underwent ultrasonographic examination, skin biopsy, and blood sampling. One spectacled bear was anesthetized, followed by euthanasia. The monitoring of the BIS in the first three bears did not contribute to obtaining more information about the degree of hypnosis, likely because of the effects of tiletamine on the brain activity. The BIS values of were always ≥65. In the bear that was euthanized, 10 minutes after administration of the lethal dose the BIS decreased to 5 (minimum, 0 to maximum, 20) and SR increased to 95 (minimum, 50 to maximum, 100). Although the BIS was not able to monitor a reliable state of hypnosis in bears anesthetized with tiletamine, zolazepam, and medetomidine, the decrease of the BIS to 5 in the euthanized bear shows that the BIS may be a reliable indicator of anesthesia depth with a different drug combination in spectacled bears. A European otter (Lutra lutra) was anaesthetized for a surgical intervention with intramuscular ketamine (15 mg/kg) and midazolam (0.5 mg/kg). Maintenance of anesthesia was performed with isoflurane and ventilation was controlled using intermittent positive pressure ventilation. Intraoperative monitoring included arterial blood pressure, pulse oximetry, capnography, and BIS. The first BIS value (50) was obtained 1 hour
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Section 1 • General
after induction of anesthesia (end-tidal isoflurane of 0.6%) coinciding with the beginning of the surgery. During the entire surgery (20 minutes), the BIS ranged between 40 and 65. The last BIS value after discontinuation of anesthesia was 74. The bispectral index has been successfully used to monitor interhemispheric asymmetry in the dolphin species Tursiops truncatus.7 The BIS device was found to be sensitive to the unihemispheric daze of the dolphin, which further encourages the use of this noninvasive monitor to study electroencephalographic changes during sleep and anesthesia in humans. An adult Eastern black rhinoceros (Diceros bicornis michaeli) was anesthetized with intramuscular etorphine (6.7 µg/kg), butorphanol (6 µg/kg), and detomidine (10 µg/kg) for a general examination. The bispectral index was used to monitor the cortical electrical activity of the rhinoceros during the 2-hour procedure. During the entire period, the BIS ranged from 85 to 97. We hypothesized that the effect of etorphine in the brain is responsible for the BIS values. A BIS reading of 95 could also be obtained in an awake Asian elephant (Elephas maximus) by applying the commercial sensors onto the skin.
CONCLUSIONS BIS readings may be obtained in a large variety of mammals, birds, and reptiles. An exception may be tortoises because of the occurrence of fluctutations between deep sedation and bursts of cerebral cortex activation. Modification of sensors to allow the subcutaneous application of needles appears important to avoid the need to shave or pluck animals and to monitor small species, which have a skull that is smaller than the human skull. The use of ketamine and etorphine may result in paradoxically elevated BIS values, but this may not be generalized and the effect may be dosedependent. Although there seems to be some indication that a BIS value between 40 and 60 coincides with a deep degree of hypnosis, there is variation. Nevertheless, an upward trend will indicate that the animal is regaining consciousness; a decrease of the BIS with an increase of SR is a critical sign and must warn the anesthetist of a potentially life-threatening condition. The interpretation of the BIS value is similar to the use of pulse oximetry, in which trends rather than
absolute values are important to evaluate the patient’s condition. Therefore, it may be concluded that BIS monitoring may be beneficial in zoo animal medicine with respect to early recovery in dangerous species and early recognition of life-threatening conditions. Further studies are needed to evaluate the BIS, especially in relation to the use of different anesthetic agents.
Acknowledgments We would like to thank Rainer Vogt and Thomas Wiestner for the modification of the BIS electrodes. REFERENCES 1. Arnemo JM, Ahlqvist P, Andersen R, et al: Risk of capture-related mortality in large free-ranging mammals: Experiences from Scandinavia. Wildl Biol 12:109–113, 2009. 2. Brodbelt DC, Blissitt KJ, MHammond RA, et al: The risk of death: The confidential inquiry into perioperative small animal fatalities. Vet Anaesth Analg 35:365–373, 2008. 3. Bruhn J, Myles PS, Sneyd R, et al: Depth of anaesthesia monitoring: What’s available, what’s validated and what’s next? Br J Anaesth 97:85–94, 2006. 4. Dahaba AA: Different conditions that could result in the bispectral index indicating an incorrect hypnotic state. Anaesth Analg 101:765–773, 2005. 5. Fernandes JA, Lutz PL, Tannenbaum A, et al: Electroencephalogram activity in the anoxic turtle brain. Am J Physiol Regul Integr Comp Physiol 273:R911–R919, 1997. 6. Haga HA, Dolvik NI: Evaluation of the bispectral index as an indicator of degree of central nervous system depression in isoflurane-anaesthetized horses. Am J Vet Res 63:438–442, 2002. 7. Howard RS, Finneran JJ, Ridgway SH: Bispectral index monitoring of unihemispheric effects in dolphins. Anesth Analg 103:626– 632, 2006. 8. Johansen JW: Update on bispectral index monitoring. Best Pract Res Clin Anaesth 20:81–99, 2006. 9. March PA, Muir WW: Bispectral analysis of the electroencephalogram: A review of its development and use in anesthesia. Vet Anaesth Analg 32:241–255, 2005. 10. Martin Jurado O: Determination of the Anaesthesia Depth in Chickens with Bispectral Index (BIS). Ph.D. Thesis, University of Zurich, Zurich, 2008. 11. Martin Jurado O, Simova-Curd S, Bettschart-Wolfensberger R, et al: Bispectral index reveals death feigning behavior in a red kite (Milvus milvus). J Avian Med Surg (in press). 12. Martin Jurado O, Vogt R, Eulenberger U, et al: Electrical activity of the brain in tortoises during brumation monitored with bispectral index (BIS). Presented at the Annual Meeting of the American Associtation of Zoo Veterinarians, Knoxville, Tennessee, October 2007. 13. Martin-Jurado O, Vogt R, Kutter A, et al: Effect of inhalation of isoflurane at endtidal concentrations greater than, equal to, and less than the minimum anesthetic concentration on bispectral index in chickens. Am J Vet Res 69:1254–1261, 2008.
19
Depth of Anesthesia Monitoring by Bispectral Analysis in Zoo Animals Jean-Michel Hatt and Olga Martin Jurado
General anesthesia is required in zoological medicine for a variety of reasons, including painful (e.g., surgery) and nonpainful interventions (e.g., radiographic examination). Typically, induction will be achieved via an injectable anesthetic, alone or as a combination. In addition to achieving analgesia and hypnosis, anesthesia in zoological medicine aims at the safe immobilization of the patient over a determined time period. Recovery time is expected to be quick, especially under field conditions, and safe both for the animal and the personnel involved. Monitoring of the patient under general anesthesia is done by a variety of tests. Some of these evaluate hemodynamic functions and autonomic nervous responses, such as heart rate, respiratory rate, blood pressure, and oxygen saturation. Others are intended to measure the depth of anesthesia (DoA) with respect to the degree of hypnosis and analgesia, including measurement of the patient’s reactions to nonphysiologic positions such as dorsal recumbency (righting reflex), corneal and pupillary reflexes, and toe pinch stimulation. In human medicine, DoA measurement is of special importance to avoid occurrence of awareness—that is, the postoperative recollection of events occurring during general anesthesia. In a recent review, incidences of awareness up to 0.2% in adults and up to 0.8% in children were reported.3 In veterinary medicine, the role of awareness cannot be assessed because animals cannot report their postanesthetic experiences. Measurement of DoA is nevertheless of interest from an animal welfare point of view. In zoological medicine, DoA monitoring is of further interest from a personnel and equipment safety point of view. However, the reliability of a stimulation test with regard to the large number of species encountered by the clinician in zoological medicine is at best adequate in relation to safety.
For safety reasons, often a lower than necessary DoA will be chosen, which only prolongs recovery but increases the dose-dependent cardiopulmonary impairment, resulting in an increase of postanesthetic morbidity and mortality. This is reflected by the high anesthetic- and sedative-related risk of death, which ranges in small mammals from 1.4% to 3.6%, in birds from 1.8% to 16.3%, and in reptiles it is 1.5%, compared with dogs and cats (0.1% to 0.2%) and humans (0.02% to 0.01%2). In wildlife anesthesia, mortalities up to 3% have been reported and it was proposed that mortalities above 2% should not be acceptable.1 Established DoA monitors include the bispectral index (BIS, Aspect Medical Systems, Norwood, Mass), the Narcotrend index (Narcotrend Monitor, Schiller AG, Baar, Switzerland), and the state entropy (SE) and response entropy (RE), derived from the spectral entropy from the electroencephalogram (EEG; M-Entropy module, GE Healthcare, Helsinki, Finland). These monitors process the level of corticocerebral activation measured by analog EEGs into a signal that reflects the DoA. The most widely used monitor is the BIS, which in 2004 was used in approximately 34% of all hospital operating rooms in the United States and 78% of teaching institutions, and had a worldwide installation base of over 25,000 units.8 Numerous studies have investigated the BIS. An Internet search on the term bispectral index anesthesia in August 2010 produced over 138,000 results, including a report on the use of the BIS in animals, including the dog, cat, horse, and goat.9 Just like any monitor, the BIS offers possibilities but also has limitations, especially with respect to various drugs. The transposition from a single-species environment such as human medicine to the multitude of species encountered in zoological medicine needs to be done with appropriate care, as with pulse oximetry. 147
148
Section 1 • General
In this chapter, we review the data from studies with BIS measurement in animals and include data on nondomestic animals obtained from studies that were carried out in our laboratory.
BISPECTRAL ANALYSIS METHODOLOGY Bispectral analysis is based on a complex statistical evaluation of human electroencephalographic data that was developed to obtain an index of the level of hypnosis. It uses a Fourier transform, an operation that transforms one complex-valued function of a real variable into another, such as time into frequency. The BIS value is represented as a dimensionless value from 0 (cortical silence) to 100 (awake) (Fig. 19-1). In humans, an
BIS 100
80
60
Awake
Light hypnotic state
Deep sedation
General anaesthesia 40
20
0
Deep hypnotic state
Increasing burst suppression
Cortical silence
Figure 19-1 The bispectral index (BIS) scale is a dimensionless scale from 0 (flatline) to 100 (awake). We used the A-2000-XP Platform Bispectral Index Monitoring System (Aspect Medical Systems, Norwood, Mass). BIS values of 65 to 85 have been recommended for a light hypnotic state, whereas values of 50 to 65 for deep sedation and values of 40 to 50 for general anesthesia are used. BIS values from 40 to 25 have been seen to produce a deep hypnotic state and, with the BIS less than 25, cortical suppression becomes more and more manifest. (From Martin Jurado O: Determination of the Anaesthesia Depth in Chickens with Bispectral Index [BIS]. Ph.D. Thesis, University of Zurich, Zurich, 2008.)
optimal degree of general anesthesia is defined as that associated with a BIS within the range of 40 to 60. In 1996, the U.S. Food and Drug Administration approved the BIS monitor as an accepted measure of the hypnotic effect of anesthetics and sedative drugs in humans. Since its introduction, BIS monitoring has gained increasing popularity in daily anesthesia practice. However, the current evidence indicates various cases of paradoxical BIS changes and inaccurate readings, which also need to be to be taken into consideration when applying the BIS in veterinary medicine (Table 19-1).4,6
TECHNIQUE AND OPTIMUM SETTING The equipment includes a monitor, a digital signal processing cable, and three electrodes with sensors. Newer models include four sensors. It is important to note that the algorithm has been constantly adapted from one model to the other. Therefore, every BIS system will yield different values and the anesthetist needs to be familiar with the system that is being used to interpret changes in values adequately. As with the use of pulse oximetry in zoo animals, the most valuable types of information are the trends indicated by the BIS. The monitor is available as stand-alone system or as an add-on module for most comprehensive patient monitoring systems. Our studies were performed with an A-2000-XP Platform Bispectral Index Monitoring System (Aspect Medical Systems). The sensors were fitted with 24-gauge needles to allow subcutaneous placement instead of the need to shave or pluck the areas, even in small animals. The impedances for sensors 1 and 3 and for sensor 2 were always <7.5 kΩ and <30 kΩ, respectively. Figure 19-2 graphically displays the location of the sensors. Based on the system we used, the different results are displayed in Figure 19-3. The main value is the BIS value, ranging from 0 (flatline or isoelectric EEG) to 100 (awake), which is displayed every 5 seconds. This represents the mean of the maximum and minimum indices of the last 15 or 30 seconds. This smoothing rate needs to be selected in the main menu. In cases of high interference, a longer smoothing rate (30 seconds) is chosen. An important additional value is the suppression ratio (SR), which is the proportion of signals over the last 63-second period for which the electroencephalographic signals are considered to be suppressed or inactive (flatline). It ranges from 0 (no suppression) to 100 (maximal suppression, or isoelectric EEG). Therefore, the lower the value, the better the signal.
Chapter 19 • Depth of Anesthesia Monitoring by Bispectral Analysis in Zoo Animals 149
TABLE 19-1 Effect of Various Factors on Bispectral Index Monitoring in Humans and Horses Effect
Anesthetic Agent Ketamine Detomidine + butorphanol Isoflurane Halothane Clinical Condition Warming blanket Hypoglycemia Hypovolemia Hypothermia Brain death Neuromuscular blocking drugs
BIS Model
BIS Change
Explanation
A-1050, A-2000 A-1000 A-1000 BIS-XP, A-1000
Paradoxical BIS ↑ BIS ↓ Paradoxical BIS ↑ High BIS
β waves ↑, δ waves ↓ In horses α, β waves ↑ Different cortical effect
A-1000, A-2000 A-2000, BIS-XP
BIS BIS BIS BIS BIS BIS
A-1050, A-1000 A-2000 A-1000, A-2000
↑ ↓ ↓ ↓ 0 ↓
Air vibration δ, θ waves ↑, α waves ↓ Cerebral perfusion ↓ Isoflurane enhancement, propofol enhancement Isoelectricity Alleviating electromyogram artifact
Data from Dahaba AA: Different conditions that could result in the bispectral index indicating an incorrect hypnotic state. Anaesth Analg 101:765-773, 2005; and Haga HA, Dolvik NI: Evaluation of the bispectral index as an indicator of degree of central nervous system depression in isofluraneanaesthetized horses. Am J Vet Res 63:438-442, 2002.
Signal quality region
A
B
Bispectral index Graphic display region
D
Figure 19-2 Placement of sensors for bispectral index monitoring in a bird (A, B) and mammal (C, D). Sensor 1 (dot) is placed between the eyes in the frontal area. Sensor 2 (circle) is placed over the temporal musculature. Sensor 3 (X) is placed immediately caudal to the eye angle. (Courtesy Jeanne Peter, Institute of Veterinary Anatomy, University of Zurich, Zurich, Switzerland.)
The quality of the EEG signal is evaluated by combining the signal quality index (SQI) and electromyography (EMG) variables. The SQI is calculated on the basis of impedance data, artifacts, and other variables. It is scaled from 0 (no quality) to 100 (maximal quality). An electromyogram is also scaled from 0 (minimal) to 100 (maximal) and indicates the power in
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Figure 19-3 Bispectral index monitor. (A-2000-XP Platform Bispectral Index Monitoring System, Aspect Medical Systems, Norwood, Mass.)
the high-frequency range, as well as muscle activity. Interference control is typically achieved by rejecting SQI values under 50% and/or electromyographic values over 50%. The electroencephalographic signal display works with a preset sweep rate of 25 mm/second and a scale of 25 µV/division.
REPTILES The determination of the DoA in reptiles is challenging, as shown in the following examples. The electrical activity of the cortex of Hermann’s tortoises (Testudo
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Figure 19-4 Bispectral index values of a Hermann’s tortoise (Testudo hermanni) during 30 minutes of the intraoperative period, from incision (T0) to the end of the surgery (T30).
hermanni) undergoing anesthesia for soft tissue surgery was evaluated. Following premedication with midazolam (2 mg/kg), butorphanol (0.4 mg/kg), and carprofen (4 mg/kg), anesthesia was induced with intravenous propofol to effect (5-10 mg/kg) and it was maintained with a 1.7% ± 0.7% expiratory fraction of isoflurane. An example of intraoperative BIS recordings is shown in Figure 19-4. In a total of seven Hermann’s tortoises, the BIS was able to display the electrical activity of the cortex during anesthesia—patterns of deep suppression (SR, 80; BIS, 15) combined with bursts of cerebral cortex activation (SR, 0; BIS, 60). This wide fluctuation has been described as a safety mechanism developed to avoid brain damage during brumation in conscious, anoxia-tolerant freshwater turtles and Hermann’s tortoises.5,12 Based on these experiences, the BIS does not seem a helpful adjunct to monitor the depth of anesthesia in chelonians. The electrical activities of the brain of anesthetized snakes (Boa constrictor) and green iguanas (Iguana iguana) have also been monitored with BIS. The first BIS values after induction of anesthesia with intravenous propofol were 70 to 90. In the following minutes and coinciding with isoflurane administration, thus increasing the depth of anesthesia, BIS values decreased to 20 to 30. Depending on titration of isoflurane during the maintenance of anesthesia, BIS values ranged from 30 to 50. Extubation occurred when the animal was considered to be able to breathe spontaneously or when movements of the limbs or the head were observed. In every case, the BIS at this time point ranged from 60 to 85. We found that extubation of the trachea based on the BIS value (BIS ≥ 60) could safely be performed.
However, very close monitoring of the patient is nevertheless recommended. The bispectral index has been found to be a very useful tool when performing anesthesia in a venomous lizard. During a coelioscopic procedure for gender determination, the bispectral index was continuously monitored in a Gila monster (Heloderma suspectum). The mean values of BIS and SR for the 25-minute isoflurane anesthesia were 25 ± 10 and 53 ± 25, respectively. No evident signs of awareness or light plane of anesthesia were observed (i.e., presence of movement, increased respiratory or heart rate). The reason for the lower BIS in the Gila monster versus the iguana and the boa is unknown. It may be hypothesized that venomous or varanid species, to which beaded lizards are related, may undergo deeper planes of anesthesia. In a specific example, the relevance of the BIS during cardiopulmonary resuscitation was assessed during the anesthetic procedure of an adult bearded dragon (Pogona vitticeps) undergoing elective neutering. After premedication with butorphanol (0.4 mg/kg) and meloxicam (0.05 mg/kg), anesthesia was induced with propofol to effect (0.5 mg/kg) and maintained with isoflurane. Intravenous access in the cephalic vein was available. The heart rate (HR) was monitored by Doppler ultrasonography and the respiratory rate (RR) was monitored by counting the excursions of the coelomic cavity. Temperature was maintained with an electric heat blanket. After induction of anesthesia, HR was 44 beats/min, RR was 6 breaths/min, the BIS was 40 and SR was 2. Twenty minutes after induction of anesthesia, the patient moved (HR, 44 beats/min; RR, 4 breaths/min; BIS, 77; SR, 0).
Chapter 19 • Depth of Anesthesia Monitoring by Bispectral Analysis in Zoo Animals 151
Fifteen minutes later, cardiorespiratory arrest occurred; the BIS was 80 and the SR was 0, perhaps related to the unpredictable shunting ability of reptiles. In the following 5 minutes, the surgery was finished while anesthesia was discontinued, ventilation was assisted, heart massage was performed, and aggressive intravenous emergency therapy was administered (atropine, 0.01 mg/kg; epinephrine, 0.02 mg/kg; doxapram, 5 mg/ kg). The mean values of BIS and SR were 90 and 0. Based on BIS (55 ± 18) and SR (13 ± 13) values, the resuscitation effort continued over 20 minutes, although no cardiorespiratory improvements were observed. Within the following 5 minutes, the BIS mean value increased to 90 ± 1 (SR, 0), the heart started to beat (HR, 44 beats/ min) and the patient was able to breathe spontaneously (RR, 4 breaths/min). Extubation of the trachea was performed and the patient recovered from anesthesia. To evaluate the validity of the BIS in bearded dragons, the euthanasia of another patient was monitored. Ten minutes after euthanasia, the BIS decreased to 3 and the SR to 100.
BIRDS The bispectral index has been successfully validated in the avian species using chickens (Gallus gallus) as experimental models.10,13 Median (range) BIS values during anesthesia were 1.75, 1.50, 1.25, 1.00, and 0.75 and the mean anesthetic concentrations of isoflurane were 25% (15% to 35%), 35% (25% to 45%), 35% (20% to 50%), 40% (25% to 55%), and 50% (35% to 65%), respectively. The median BIS value at extubation was 70 ± 9. Blood pressure changed with end-tidal isoflurane concentrations, whereas the heart rate did not. Based on this validation study, the BIS has been further used in clinical avian patients as additional monitoring to assess the degree of hypnosis. Satisfactory results have been obtained in a large variety of orders, such as Anseriformes, Ciconiiformes, Psittaciformes, Falconiformes, and Strigiformes. In an interesting case, the BIS was able to uncover feigning death behavior in a red kite (Milvus milvus) during recovery from isoflurane anesthesia.11 The bispectral index ranged from 44 to 57 during maintenance of isoflurane anesthesia and, at the moment of extubation of the trachea, the BIS was 59. The index rose up to 85 in 1 minute while the kite remained immobile in sternal recumbence. The bird was perched, keeping the upright position. Whereas behavioral or cardiorespiratory variables remained unchanged, the BIS revealed that the bird had regained consciousness.
MAMMALS The anesthesia of three gelada baboons (Theropithecus gelada) for a general examination, tuberculin testing, and radiographic examination were monitored with the BIS. An adequate degree of hypnosis to approach the geladas was achieved after a combination of intramuscular ketamine (5 mg/kg) and medetomidine (0.07 mg/ kg) was administered. During the following 15 minutes, manipulations were carried out without episodes of apparent consciousness while the BIS ranged from 30 to 65. Following reversal with atipamezole, the BIS increased to 97 in the following 8 minutes, coinciding with eye blinking and twitching of facial muscles. Future anesthetic episodes in geladas will benefit from additional monitoring with the BIS because it would increase patient and staff safety (e.g., administration of additional anesthetic drugs before slight movement occurs). The device was able to display a highly accurate state of hypnosis in the presented cases reliably. Similar results were obtained in an orangutan (Pongo pygmaeus) anesthetized with intramuscular ketamine (5 mg/kg) and xylazine (3 mg/kg). Four adult spectacled bears (Tremarctos ornatus) were anesthetized with tiletamine and zolazepam (1.1 to 1.7 mg/kg), and medetomidine (0.06 to 0.1 mg/kg). Three of the bears underwent ultrasonographic examination, skin biopsy, and blood sampling. One spectacled bear was anesthetized, followed by euthanasia. The monitoring of the BIS in the first three bears did not contribute to obtaining more information about the degree of hypnosis, likely because of the effects of tiletamine on the brain activity. The BIS values of were always ≥65. In the bear that was euthanized, 10 minutes after administration of the lethal dose the BIS decreased to 5 (minimum, 0 to maximum, 20) and SR increased to 95 (minimum, 50 to maximum, 100). Although the BIS was not able to monitor a reliable state of hypnosis in bears anesthetized with tiletamine, zolazepam, and medetomidine, the decrease of the BIS to 5 in the euthanized bear shows that the BIS may be a reliable indicator of anesthesia depth with a different drug combination in spectacled bears. A European otter (Lutra lutra) was anaesthetized for a surgical intervention with intramuscular ketamine (15 mg/kg) and midazolam (0.5 mg/kg). Maintenance of anesthesia was performed with isoflurane and ventilation was controlled using intermittent positive pressure ventilation. Intraoperative monitoring included arterial blood pressure, pulse oximetry, capnography, and BIS. The first BIS value (50) was obtained 1 hour
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after induction of anesthesia (end-tidal isoflurane of 0.6%) coinciding with the beginning of the surgery. During the entire surgery (20 minutes), the BIS ranged between 40 and 65. The last BIS value after discontinuation of anesthesia was 74. The bispectral index has been successfully used to monitor interhemispheric asymmetry in the dolphin species Tursiops truncatus.7 The BIS device was found to be sensitive to the unihemispheric daze of the dolphin, which further encourages the use of this noninvasive monitor to study electroencephalographic changes during sleep and anesthesia in humans. An adult Eastern black rhinoceros (Diceros bicornis michaeli) was anesthetized with intramuscular etorphine (6.7 µg/kg), butorphanol (6 µg/kg), and detomidine (10 µg/kg) for a general examination. The bispectral index was used to monitor the cortical electrical activity of the rhinoceros during the 2-hour procedure. During the entire period, the BIS ranged from 85 to 97. We hypothesized that the effect of etorphine in the brain is responsible for the BIS values. A BIS reading of 95 could also be obtained in an awake Asian elephant (Elephas maximus) by applying the commercial sensors onto the skin.
CONCLUSIONS BIS readings may be obtained in a large variety of mammals, birds, and reptiles. An exception may be tortoises because of the occurrence of fluctutations between deep sedation and bursts of cerebral cortex activation. Modification of sensors to allow the subcutaneous application of needles appears important to avoid the need to shave or pluck animals and to monitor small species, which have a skull that is smaller than the human skull. The use of ketamine and etorphine may result in paradoxically elevated BIS values, but this may not be generalized and the effect may be dosedependent. Although there seems to be some indication that a BIS value between 40 and 60 coincides with a deep degree of hypnosis, there is variation. Nevertheless, an upward trend will indicate that the animal is regaining consciousness; a decrease of the BIS with an increase of SR is a critical sign and must warn the anesthetist of a potentially life-threatening condition. The interpretation of the BIS value is similar to the use of pulse oximetry, in which trends rather than
absolute values are important to evaluate the patient’s condition. Therefore, it may be concluded that BIS monitoring may be beneficial in zoo animal medicine with respect to early recovery in dangerous species and early recognition of life-threatening conditions. Further studies are needed to evaluate the BIS, especially in relation to the use of different anesthetic agents.
Acknowledgments We would like to thank Rainer Vogt and Thomas Wiestner for the modification of the BIS electrodes. REFERENCES 1. Arnemo JM, Ahlqvist P, Andersen R, et al: Risk of capture-related mortality in large free-ranging mammals: Experiences from Scandinavia. Wildl Biol 12:109–113, 2009. 2. Brodbelt DC, Blissitt KJ, MHammond RA, et al: The risk of death: The confidential inquiry into perioperative small animal fatalities. Vet Anaesth Analg 35:365–373, 2008. 3. Bruhn J, Myles PS, Sneyd R, et al: Depth of anaesthesia monitoring: What’s available, what’s validated and what’s next? Br J Anaesth 97:85–94, 2006. 4. Dahaba AA: Different conditions that could result in the bispectral index indicating an incorrect hypnotic state. Anaesth Analg 101:765–773, 2005. 5. Fernandes JA, Lutz PL, Tannenbaum A, et al: Electroencephalogram activity in the anoxic turtle brain. Am J Physiol Regul Integr Comp Physiol 273:R911–R919, 1997. 6. Haga HA, Dolvik NI: Evaluation of the bispectral index as an indicator of degree of central nervous system depression in isoflurane-anaesthetized horses. Am J Vet Res 63:438–442, 2002. 7. Howard RS, Finneran JJ, Ridgway SH: Bispectral index monitoring of unihemispheric effects in dolphins. Anesth Analg 103:626– 632, 2006. 8. Johansen JW: Update on bispectral index monitoring. Best Pract Res Clin Anaesth 20:81–99, 2006. 9. March PA, Muir WW: Bispectral analysis of the electroencephalogram: A review of its development and use in anesthesia. Vet Anaesth Analg 32:241–255, 2005. 10. Martin Jurado O: Determination of the Anaesthesia Depth in Chickens with Bispectral Index (BIS). Ph.D. Thesis, University of Zurich, Zurich, 2008. 11. Martin Jurado O, Simova-Curd S, Bettschart-Wolfensberger R, et al: Bispectral index reveals death feigning behavior in a red kite (Milvus milvus). J Avian Med Surg (in press). 12. Martin Jurado O, Vogt R, Eulenberger U, et al: Electrical activity of the brain in tortoises during brumation monitored with bispectral index (BIS). Presented at the Annual Meeting of the American Associtation of Zoo Veterinarians, Knoxville, Tennessee, October 2007. 13. Martin-Jurado O, Vogt R, Kutter A, et al: Effect of inhalation of isoflurane at endtidal concentrations greater than, equal to, and less than the minimum anesthetic concentration on bispectral index in chickens. Am J Vet Res 69:1254–1261, 2008.